The NCI Office of the Director (OD) proposes a Human Tumor Atlas pilot project in response to the Blue Ribbon Panel (BRP) recommendations issued as part of the Beau Biden Cancer MoonshotSM Initiative. Upon its completion, the Human Tumor Atlas will offer a comprehensive description of the dynamics of the molecular, cellular, and physiological events associated with individual tumor cells, the tumor mass itself, the tissue of origin, and sites of metastases. The Human Tumor Atlas pilot project should provide a foundation on which larger scale atlas efforts may be constructed, including development of standard operating procedures (SOPs) that address challenges associated with acquisition of high quality normal and tumor tissue across research sites, reliable and robust data collection, including quality control metrics, and community-accessible data. Ideally, the Human Tumor Atlas pilot project will inform future data collection by determining which single-cell analysis strategies are maximally informative with respect to describing the heterogeneous states and spatial distribution of tumor and non-tumor cells, including immune cells, stromal components, and complementary cancer-derived biomaterials. The resulting pilot-scale tumor atlas should facilitate predictive modeling of cancer by the scientific community to aid in the understanding of mechanisms underlying pediatric cancer and metastatic breast cancer.